Potassium Hydroxide → 2-(6-methoxy-1H-inden-3-yl)butanoic acid

HRID 603374Notes

Reaction equation

HRID 603374 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH:12]([CH2:17][CH3:18])[C:13]([O:15]C)=[O:14])=[CH:8][CH2:9]2)=[CH:5][CH:4]=1.[OH-].[K+]>CO.O>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH:12]([CH2:17][CH3:18])[C:13]([OH:15])=[O:14])=[CH:8][CH2:9]2)=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 14797Potassium Hydroxide2×HCID 11402344Methyl 2-(6-methoxy-1H-inden-3-yl)butanoate

Product 1

HCID 112532602-(6-methoxy-1H-inden-3-yl)butanoic acidYield 93%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of the ester prepared in Example 18 (200.0 g, 813 mmol) in MeOH (2 L), was added a solution of KOH (91.0 g, 1.63 mol) in water (200 mL). The reaction mixture was stirred at 60° C. (internal temperature) for 2 h. TLC showed 70% conversion. A solution of KOH (45.0 g, 0.81 mol) in water (100 mL) was then slowly added to the reaction mixture. The reaction was complete in 1 h, after which the mixture was cooled to rt, and then the solvents were removed under reduced pressure. The residue was dissolved in water (3 L), and then washed with EtOAc (2×1 L). The aqueous layer was cooled in an ice-water bath, acidified with HCl (37% aqueous solution) to pH<3.0 and extracted with CH2Cl2 (3 L). The organic phase was washed with water (2×1 L), dried over Na2SO4, filtered, and then the filtrate was stirred with 30 g charcoal for 2 h. The charcoal was removed by filtration through a pad of Celite® to provide the title compound (175 g, 93%) as a light brown solid after solvent removal and drying under reduced pressure. 1H NMR (300 MHz), (DMSO-d6) δ12.20 (b, 1H), 7.30 (d, 1H), 7.06 (d, 1H), 6.82 (dd, 1H), 6.22 (s, 1H), 3.75 (s, 3H), 3.45 (t, 1H), 3.30 (s, 2H), 1.90 (m, 1H), 1.78 (m, 1H), 0.90 (t, 3H).

Workup

  1. waitThe reaction was complete in 1 h
  2. temperatureafter which the mixture was cooled to rt
  3. customthe solvents were removed under reduced pressure
  4. dissolutionThe residue was dissolved in water (3 L)
  5. washwashed with EtOAc (2×1 L)
  6. temperatureThe aqueous layer was cooled in an ice-water bath
  7. extractionextracted with CH2Cl2 (3 L)
  8. washThe organic phase was washed with water (2×1 L)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. stirringthe filtrate was stirred with 30 g charcoal for 2 h
  12. customThe charcoal was removed by filtration through a pad of Celite®

Sources & evidence

ORD record
ord-c7cd845b07874312b309b8062a7005f4
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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